The long-term objectives of the proposed research are: (1) to learn more about human ocular motor disorders that impair vision during everyday activities;(2) to apply insights from basic science to better understand clinical problems (a translational approach);and (3) to appraise therapeutic measures for abnormal eye movements and so restore clear vision. There are five specific aims, which grow out of prior studies: The first project addresses the pathogenesis of disorders such as opsoclonus, and models that attribute these ocular oscillations to either cerebellar or brainstem mechanisms. The second project investigates the velocity profiles of rapid eye movements (saccades), which are disrupted in certain disorders affecting the brainstem and cerebellum due to premature termination of these movements. The third project concerns the way in which saccades and vergence movements interact during natural shifts of the fixation point. Using a novel paradigm, it is possible to dissociate in time the saccadic and vergence components, and thus systematically study their interaction. The fourth project addresses how vestibular eye movements are suppressed while viewing a near, head fixed target (as in reading while walking). The goal is to better understanding disability for such tasks in patients with disorders of vestibular or visually mediated eye movements. The fifth project is a crossover evaluation of memantine and gabapentin as treatment for acquired forms of nystagmus. Gabapentin suppresses acquired nystagmus and improves vision in some patients, but side-effects such as ataxia limit the dosage tolerated. Memantine is also reported to suppress pendular nystagmus and improve vision in multiple sclerosis (MS), but no double-masked trial has been performed. The research strategies are (1) to relate reliable measurements of eye movements to visual complaints of patients during natural behaviors;(2) to use measurements of normal and abnormal eye movements to test mathematical models that are biologically plausible;and (3) to evaluate new treatments of disorders of ocular motility using controlled trials. Thus, these projects will provide new information on the pathogenesis and treatment of a range of common disorders of eye movements that disrupt clear vision.